TDO2

tryptophan 2,3-dioxygenase

Basic information

Region (hg38): 4:155854738-155920406

Links

ENSG00000151790 ∙ NCBI:6999 ∙ OMIM:191070 ∙ HGNC:11708 ∙ Uniprot:P48775 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial hypertryptophanemia (Supportive), mode of inheritance: AR
• familial hypertryptophanemia (Limited), mode of inheritance: Unknown
• familial hypertryptophanemia (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypertryptophanemia	AD	General	The clinical relevance of the condition is unclear	Biochemical	28285122

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TDO2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TDO2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	1	3
missense			16	1	2	19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	16	3	3

Variants in TDO2

This is a list of pathogenic ClinVar variants found in the TDO2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-155863483-C-T		not specified	Likely benign (Mar 29, 2022)
4-155863497-A-G		not specified	Uncertain significance (Jun 07, 2024)
4-155863499-T-C		not specified	Uncertain significance (Apr 22, 2024)
4-155863508-A-G		ASIC5-related disorder	Likely benign (May 10, 2023)
4-155863515-T-C		not specified	Uncertain significance (Jun 24, 2022)
4-155863547-C-T		not specified	Uncertain significance (Mar 29, 2024)
4-155863558-C-G		not specified	Uncertain significance (Nov 16, 2022)
4-155863689-T-C		not specified	Uncertain significance (Feb 07, 2023)
4-155863694-C-T		not specified	Uncertain significance (Jul 06, 2021)
4-155863697-T-C		not specified	Uncertain significance (Nov 17, 2023)
4-155863703-G-A		not specified	Uncertain significance (Jan 03, 2024)
4-155863716-G-A		not specified	Uncertain significance (May 30, 2024)
4-155863728-G-C		not specified	Uncertain significance (May 20, 2024)
4-155863730-C-A		ASIC5-related disorder	Likely benign (Jul 12, 2023)
4-155903763-G-C		not specified	Uncertain significance (Oct 13, 2023)
4-155904051-C-A		not specified	Uncertain significance (May 08, 2024)
4-155905097-C-A		not specified	Uncertain significance (May 25, 2022)
4-155907791-A-G		not specified	Uncertain significance (Nov 19, 2022)
4-155908907-G-C		Familial hypertryptophanemia	Pathogenic (Oct 04, 2017)
4-155908924-G-A		not specified	Uncertain significance (Jan 26, 2022)
4-155908938-T-C			Benign (Dec 31, 2019)
4-155908959-G-C		not specified	Uncertain significance (Mar 26, 2024)
4-155908993-C-T		not specified	Uncertain significance (Aug 02, 2021)
4-155910047-G-A		not specified	Uncertain significance (Oct 12, 2021)
4-155910082-C-CA		Familial hypertryptophanemia	Pathogenic (Oct 04, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TDO2	protein_coding	protein_coding	ENST00000536354	12	65669

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.04e-10	0.646	125653	1	94	125748	0.000378

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.221	210	201	1.04	0.00000987	2651
Missense in Polyphen		91	72.899	1.2483		952
Synonymous	-0.303	77	73.7	1.04	0.00000357	718
Loss of Function	1.40	19	26.8	0.708	0.00000156	316

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000689	0.000689
Ashkenazi Jewish	0.00	0.00
East Asian	0.000331	0.000326
Finnish	0.000193	0.000185
European (Non-Finnish)	0.000483	0.000466
Middle Eastern	0.000331	0.000326
South Asian	0.000307	0.000261
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Heme-dependent dioxygenase that catalyzes the oxidative cleavage of the L-tryptophan (L-Trp) pyrrole ring and converts L- tryptophan to N-formyl-L-kynurenine. Catalyzes the oxidative cleavage of the indole moiety. {ECO:0000255|HAMAP-Rule:MF_03020, ECO:0000269|PubMed:25066423, ECO:0000269|PubMed:27762317, ECO:0000269|PubMed:28285122}.
• Disease: DISEASE: Hypertryptophanemia (HYPTRP) [MIM:600627]: An autosomal recessive condition characterized by persistent hypertryptophanemia and hyperserotoninemia. {ECO:0000269|PubMed:28285122}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tryptophan metabolism - Homo sapiens (human);Tryptophan Metabolism;NAD Biosynthesis II (from tryptophan);NAD+ biosynthetic pathways;Amino Acid metabolism;Tryptophan metabolism;Monoamine Transport;Tryptophan catabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde;Metabolism;L-kynurenine degradation;NAD <i>de novo</i> biosynthesis;Tryptophan degradation;superpathway of tryptophan utilization;tryptophan degradation (Consensus)

Recessive Scores

• pRec: 0.359

Intolerance Scores

• loftool: 0.387
• rvis_EVS: 0
• rvis_percentile_EVS: 53.73

Haploinsufficiency Scores

• pHI: 0.102
• hipred: N
• hipred_score: 0.251
• ghis: 0.449

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.754

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tdo2
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); pigmentation phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); vision/eye phenotype

Gene ontology

• Biological process: tryptophan catabolic process;tryptophan catabolic process to kynurenine;tryptophan catabolic process to acetyl-CoA;protein homotetramerization;oxidation-reduction process;response to nitroglycerin
• Cellular component: cytosol
• Molecular function: tryptophan 2,3-dioxygenase activity;protein binding;amino acid binding;oxygen binding;heme binding;identical protein binding;metal ion binding